It is not every day you happen to stumble serendipitously upon a potential answer to one of regenerative medicine’s most significant obstacles – how to generate cellular scaffolding for tissue engineering. But that is exactly what researchers at the University of Washington have inadvertently discovered.

Torso with liver highlightedShare on Pinterest
The new technique could be used to decellularize tissues for tissue engineering and regenerative medicine.

Regenerative medicine is a game-changing area of medicine with the potential to heal damaged tissues and organs, offering solutions and hope for people who have conditions that are currently beyond repair. However, in order to use stem cells to generate new tissue or organs, there needs to be a support network to function as a structural shell.

Strategies in the field of tissue engineering and regenerative medicine often employ 3D scaffolds to mimic the natural extracellular matrix. This matrix is used as structural template that supports cell adhesion, migration, differentiation and proliferation, and provides guidance for neo-tissue formation.

The University of Washington team encountered the new technique to fashion a natural cellular scaffold for regenerative medicine while testing a method to eliminate cancerous tumors.

The researchers were studying boiling histotripsy – a technique that uses millisecond-long bursts of high-intensity ultrasound waves to break apart tissue – as a mode to liquefy cancer tumors with ultrasound waves.

Boiling histotripsy lesions were produced in a bovine liver with a clinical 1.2 MHz MR-HIFU system (Sonalleve, Philips, Finland), using 30 10-ms pulses and pulse repetition frequencies of 1-10 Hz. Peak acoustic powers corresponding to estimated in situ shock front amplitude of 65 MPa were used.

The researchers explain that high power sound waves below 20 Hz, the lower frequency limit of human hearing, are felt in the body but not heard by the human ear as sound.

Subsequent to the destruction of the tumors by sound, the body should eradicate them from the body as cellular waste. However, on examination of the “decellularized” tissues, the boiling had left a fibrous framework intact.

Yak-Nam Wang, a senior engineer at the University of Washington’s Applied Physics Laboratory, says:

In some of our experiments, we discovered that some of the stromal tissue and vasculature was being left behind. So we had the idea about using this to decellularize tissues for tissue engineering and regenerative medicine.”

The framework that remains after decellularizing tissues is identified as the extracellular matrix, a fibrous network that offers a scaffold for the growing cells.

a cross section through a histotripsy lesionShare on Pinterest
A cross section through a histotripsy lesion created in bovine liver tissue. The liquefied cellular contents are washed out, revealing the remaining extracellular matrix.
Image credit: T.Khoklova

Decellularizing tissues and organs often involve the use of chemical and enzymatic treatments. This method takes multiple days and can cause damage to tissues and fibers.

Histotripsy, on the other hand, exercises fast decellularization of tissue with minimal damage to the matrix.

“In tissue engineering, one of the holy grails is to develop biomimetic structures so that you can replace tissues with native tissue,” Wang explains.

“Stripping away cells from already developed tissue could provide a good candidate for these structures since the extracellular matrix already acts as the cellular framework for tissue systems,” he adds.

Due to the bare skeleton-like composition of the matrix, only a weak immune response is induced from the host. Theoretically, the matrix could be nourished with stem cells from the person to effectively re-grow an organ.

“The other thought is that maybe you could just implant the extracellular matrix and then the body itself would self-seed the tissues, if it’s just a small patch of tissue that you’re replacing,” Wang theorizes. “You won’t have any immune issues, and because you have this biomimetic scaffold that’s closer to the native tissue, healing would be better, and the body would recognize it as normal tissue.”

The technique, presented at the 168th meeting of the Acoustical Society of America, held October 27-31, 2014, at the Indianapolis Marriott Downtown Hotel, IN, could open many doors for regenerative medicine.

Wang’s current investigations revolve around decellularization of kidney and liver tissue from large animals. Future work for the team involves increasing the size of the decellularized tissues and assessing their in-vivo regenerative efficacy.

Medical News Today recently reported that scientists reset human stem cells, in what was called a “significant milestone” in medicine. Scientists have discovered how to successfully “reset” human pluripotent stem cells to the earliest developmental state, equivalent to cells found in an embryo before it implants in the womb (7-9 days old).